While spinal manipulation is widely seen as a reasonable treatment option for biomechanical disorders of the spine, such as neck pain and low back pain, the use of spinal manipulation to treat non-musculoskeletal complaints remains controversial. This controversy is due in part to the perception that there is no robust neurobiological rationale to justify using a biomechanical treatment of the spine to address a disorder of visceral function. This paper therefore looks at the physiological evidence that spinal manipulation can impact visceral function. A structured search was conducted, using PubMed and the Index to Chiropractic Literature, to construct of corpus of primary data studies in healthy human subjects of the effects of spinal manipulation on visceral function. The corpus of literature is not large, and the greatest number of papers concerns cardiovascular function. Authors often attribute visceral effects of spinal manipulation to somato-autonomic reflexes. While this is not unreasonable, little attention is paid to alternative mechanisms such as somato-humoural pathways. Thus, while the literature confirms that mechanical stimulation of the spine modulates some organ functions in some cohorts, a comprehensive neurobiological rationale for this general phenomenon has yet to appear.

From the FULL TEXT Article:

Introduction

Spinal manipulation is generally accepted as one reasonable
treatment option in the management of musculoskeletal disorders
such as low back pain and neck pain. Some evidence also exists
that certain visceral disorders benefit from spinal manipulation
(for example, see Bakris et al., 2007). However, the mechanisms
by which spinal manipulation might alter visceral function, and
so impact visceral disease, remain unclear. Therefore, in this paper,
we review the currently available literature concerning visceral responses
to the application of mechanical stimuli to the spine and
paraspinal tissues. We specifically draw from human studies using
high velocity, low amplitude manipulations, and also from research
using biomechanically similar manoeuvres. Therefore, in
this paper, the term ‘spinal manipulation’ may be interpreted liberally
to include a range of related procedures.

To provide some clinical context for this review, it is to be noted
that only a relatively small percentage of patients receive spinal
manipulation specifically for the management of a non-musculoskeletal
complaint. Numbers vary somewhat from survey to survey,
but in Denmark, for example, the proportion of all patients presenting
to chiropractors with non-musculoskeletal complaints apparently
fell from 7% in 1966 to 3% in 1999 (Hartvigsen et al., 2003).
Furthermore, the range of non-musculoskeletal complaints reported
to be treated with spinal manipulation is quite limited. In fact, a previous
review found that approximately half of the case reports and
case series dealing with manipulative management of non-musculoskeletal
complaints pertained to only a handful of disorders
including gynecological complaints, visual deficits, asthma and
enuresis (Budgell, 1999). Clinical trials of spinal manipulation in
the treatment of non-musculoskeletal disorders are similarly restricted
with the bulk of studies focused on cardiovascular disease,
gynecological complaints, infantile colic and asthma (Hawk et al.,
2007; Nakayama and Budgell, 2009). Given the restricted interests
of clinical reports and controlled studies, as described above, we will
therefore review basic physiological studies of what appear to be the
most clinically relevant phenomena: cardiovascular, respiratory,
gastrointestinal and female reproductive function.

Titles of identified articles were reviewed to eliminate studies
which were either clearly off-topic, not published in English or
which did not appear to report original data (reviews, commentaries
etc.). The abstracts were then reviewed for the articles which
passed the first filtering process. The abstracts were further reviewed
for the additional criteria that the articles reported original
studies in healthy humans of physiological responses to manual
treatment (spinal manipulation or mobilization) of the spine. Articles
which satisfied these criteria (Figure 1) were obtained as full text
for data extraction and synthesis in this review.

Additionally, articles held in the authors’ own collections but
which were not identified by the electronic searches were included
in this review if they satisfied the inclusion criteria. These
have been marked with an asterisk in their respective tables and
included nine articles pertaining to humoural or neurological responses
to manipulation, 15 articles pertaining to cardiovascular
responses, and one article each pertaining to respiratory and gastrointestinal
function. On reading the full texts, some articles
were excluded because it became apparent that the subjects were
symptomatic patients. The sum of the numbers of articles located
with each of the five searches does not equal the total number of
articles subsequently analyzed since there was some duplication
of results. That is to say that some studies investigated outcomes
from more than one system, for example both cardiovascular and
respiratory.

Results

Studies of cardiovascular function

Perhaps because of the limitations of available technology to record
other physiological parameters and due to clinical relevance,
the largest number of experimental studies of spinal manipulation
and somato-visceral effects in humans has examined outcomes in
cardiovascular function. A total of 18 articles which satisfied our
inclusion criteria were retrieved (Table 1). The cardiovascular measures
commonly reported were heart rate (HR), blood pressure (BP)
and heart rate variability (HRV), from which changes in autonomic
output to the heart may be implied. Earlier studies of effects of
spinal manipulation on heart rate and blood pressure have employed
less reliable technology. For example, in studies of effects
of SMT on blood pressure in healthy young cohorts, McKnight
and DeBoer (1988) and Tran and Kirby (1977a,b) employed single
before and after measures obtained by auscultatory sphygmomanometry,
whereas Nansel et al., using a similar cohort, did not describe
their methods of measuring heart rate or blood pressure
(Nansel et al., 1991). Automated methods of monitoring blood
pressure and heart rate are demonstrably more reliable than manual
methods (for example, see Pastellides, 2009). Earlier studies
may also have eschewed statistical analysis of results in favor of
the authors’ subjective opinion of what constituted an important
effect (for example, see Tran and Kirby, 1977a,b). Therefore, this review
only considers in detail those studies that define both the
outcome measure and statistical analysis used.

Figure 1.
Methods and results of searches in
PubMed and Index of Chiropractic Literature (ICL).

Table 1.
Studies of cardiovascular function.

A few studies have employed arterial tonometry, a method
which uses a force transducer placed over an artery to continuously
measure blood pressure and, from the frequency of the pulse
waves, heart rate. The tonometry equipment is costly but technically
simple to apply and is a conventional method for monitoring
blood pressure during surgery. The first pilot study using arterial
tonometry to measure responses to spinal manipulation reported
no significant changes or slight decreases in heart rate and blood
pressure in alert healthy subjects (n = 11) receiving a series of
mechanical cervical stimuli: direct pressure to cervical muscles,
slow passive rotations of the neck and high velocity low amplitude
manipulations, all of which were characterized as innocuous by the
subjects (Fujimoto et al., 1999). Of these stimuli, cervical spinal
manipulation produced the largest effects: decreases in systolic
and diastolic pressures of 6.8 (S.D. ±1.9) mmHg and 6.6 (S.D.
±2.1) mmHg, respectively. While the authors of this study speculated
that the cardiovascular changes seen were mediated primarily
via the autonomic nervous system, they did not perform
calculations in the time or frequency domains, for example power
spectrum analysis, on their blood pressure and heart rate data
which would have given some quantitative measure of changes in
autonomic output to the cardiovascular system. Using a more complex
design, four treatment paradigms over four successive days
with measures of blood pressure pre-treatment and at 5, 15 and
30 min post treatment, Pastellides (2009) consistently showed decreases
in systolic blood pressure in response to upper cervical
manipulation, thoracic manipulation, and combined cervical and
thoracic manipulation. Interestingly, McGuiness et al. (1997) referred
to an increase in heart rate, and systolic and diastolic blood
pressure following a ‘grade III posteroanterior mobilization’,
although their paper does not report the actual data on heart rate
and blood pressure.

While heart rate is a commonly used outcome measure, it is not
constant even in a resting subject, but varies over a narrow range
largely in response to changes in autonomic output to the cardiovascular
system. Consequently analysis of heart rate variability
has been used to indirectly assess relative autonomic drive to the
heart (Task Force of the European Society of Cardiology and the
North American Society of Pacing and Electrophysiology, 1996).
To explain the physiological mechanisms in brief, in humans relatively
fast oscillations in heart rate, in the range of 0.25 Hz, are driven
by the respiratory cycle (Grossman et al., 2004): as we inhale,
thoracic pressure decreases, drawing blood pressure down slightly,
in response to which baroreflexes attenuate vagal output to the
heart somewhat, thereby permitting a slight rise in heart rate.
The reverse process occurs as we exhale. Thus the relatively fast
oscillations in heart rate reflect parasympathetic (vagal) output
to the heart. Slower oscillations in heart rate, in the range of
0.15 Hz and lower, reflect a systemic ebbing and flowing of sympathetic
output to the blood vessel walls creating low amplitude
oscillations in blood pressure which again feed through the barore-
flexes to modulate vagal tone. Thus, the slower oscillations in heart
rate are ultimately driven by sympathetic tone but are dependent
upon the integrity of the parasympathetic nervous system (Grasso
et al., 1997). Nonetheless, computer algorithms can discriminate
between fast and slow oscillations in R–R interval and generate
numerical values which are broadly representative of sympathetic
and parasympathetic cardiac tone.

Hence, based on HRV calculated from ECG recordings in healthy,
pain-free young adults, it was reported that both cervical (Budgell
and Hirano, 2001) and thoracic (Budgell and Polus, 2006) spinal
manipulation were associated with increases in sympathetic output
to the heart, even as heart rate decreased somewhat. Changes in
HRV, and so autonomic output to the heart, have also been reported
with lumbar manipulation (Roy et al., 2009). However, the small increases
reported in parasympathetic tone in subjects without low
back pain barely achieved the level of statistical significance.

Hence, while the numbers of studies and the sizes of their cohorts
have been modest, there is some evidence that, in healthy
subjects, high-velocity low-amplitude manipulation of the cervical,
thoracic or lumbar spine modulates autonomic output to the heart.
Cervical and thoracic manipulation have been associated with no
changes or a shift in favor of sympathetic output to the heart in
healthy young adults. Lumbar manipulation was associated with
a small increase in cardiac parasympathetic output. Both cervical
and thoracic manipulation have been associated with changes in
heart rate and blood pressure. The actual magnitudes of changes
in heart rate and blood pressure in the reports cited thus far have
been modest – single digit decreases in HR (bpm), and systolic and
diastolic blood pressures (mmHg) – and, in the healthy subjects
employed, of course, of no clinical significance (but see Koch et al.,
2002).

A number of authors have also reported effects of spinal
manipulation on peripheral vascular physiology. Outcome measures
have included such parameters as

Cervical
mobilization has been associated with no (Chiu and Wright,
1996) or small (Vicenzino et al., 1998) decreases in skin temperature
and blood flux (Vicenzino et al., 1998). Interestingly, Harris
and Wagnon (1987) reported increases in hand skin temperature
using what was likely a higher velocity manipulation (vs. Chiu
and Wright’s and Vicenzino’s mobilization) of the cervical spine.
Karason and Drysdale (2003) showed mixed results, with lumbar
manipulation resulting in decreased blood flow in the dorsum of
the foot in non-smoking subjects.

In earlier studies, effects of
manipulation on skin temperature have been interpreted based
on the assumption that an increase in skin temperature reflected
vasodilation driven by decreased sympathetic output to dermal
blood vessels. This assumption is now known to be overly simplistic
(see Hodges and Johnson, 2009), so that skin temperature
and skin blood flow measurements cannot be regarded as surrogates
for direct measurement of autonomic output. Hence, while
it may be said with some confidence that spinal manipulation can
affect peripheral cutaneous blood flow in certain cohorts, the
underlying mechanisms remain to be resolved and there is no
obvious explanation for why different studies should report
changes of the opposite polarity (see Harris and Wagnon, 1987
vs. Vicenzino et al., 1998).

One published study used single photon emission computed
tomography to examine the effects of spinal manipulation on central
nervous system blood flow (Cagnie et al., 2005). No raw data
were presented, but the authors stated that in a cohort of 15 subjects
it was possible to identify one region of the cerebellum
where blood flow decreased when recorded 30 min after a cervical
spinal manipulation. The physiological significance of this
finding is not clear, and no correlation could be drawn with
symptomatology in what was, after all, a healthy cohort. The
authors suggest, however, that cerebellar hypoperfusion could
be one source of subjective side effects following spinal manipulation
(Cagnie et al., 2005).

Studies of respiratory function

In comparison to the number of studies of cardiovascular function,
investigations of the effects of spinal manipulation on respiratory
function are rather sparse; only three papers were found
which satisfied the inclusion criteria (Table 2). McGuiness et al. referred
to an increase in respiratory rate following a ‘grade III posteroanterior
mobilization’ (McGuiness et al., 1997), although
their paper did not report the actual pre- and post-treatment respiratory
rates. A study of an apparently well cohort of adults demonstrated
that a 2 week course of upper cervical manipulation was
associated with statistically significant increases in forced vital
capacity of approximately 6% and forced expiratory volume of
approximately 5%, although this study also had no control cohort
(Kessinger, 1997). A small study with only five subjects in the
intervention group also referred to increases in FVC and FEV-1 with
manipulation (Engel and Vemulpad, 2007), but did not report the
data on which these results were apparently based. The existing
literature therefore is essentially phenomenological and provides
little meaningful data about the effects of spinal manipulation on
respiratory function in humans (but see, for example, Koch et al.,
1998).

Studies of gastrointestinal function

Notwithstanding the interest by practitioners in the effects of
spinal manipulation on gastrointestinal function, basic physiological
studies are all but absent (Table 3). One small study (13 trials in
four subjects) reported that gastric tone, as determined by electrogastrogram
wave amplitude, increased in response to upper cervical
manipulation (6 trials) and in comparison to trials in which
subjects (7 trials) did not receive spinal manipulation (Wiles,
1980). Raw data and the statistical methods for pre- vs. postSMT
comparisons were not described in detail.

Table 2.
Studies of respiratory function.

Table 3.
Studies of gastrointestinal function

Studies of female reproductive function

Our systematic searches of PubMed and the Index to Chiropractic
Literature revealed only one study of spinal manipulation in humans
with implications for female reproductive function (Table 4).
Nogueira de Almeida et al. (2010) examined the effects of sacral
manipulation on intravaginal and basal perineal tonus. In this
uncontrolled, single cohort trial, manipulation was associated with
increased phasic perineal contraction amplitude.

Human studies of somato-autonomic reflexes

Somato-autonomic reflexes are often invoked as the mechanisms
underlying somato-visceral phenomena associated with
spinal manipulative therapy. Therefore, to do justice to the topic
of spino-visceral phenomena, it is also appropriate to review studies
of changes in autonomic function, and changes in organ or tissue
function which are reflective of autonomic activity but which
do not yet have any clear clinical implications. Five papers which
satisfied the inclusion criteria were identified (Table 5).

sweating, which has been measured indirectly by skin
conductance (see for example, Moulson and Watson, 2006; Jowsey
and Perry, 2010),

static pupil diameter (Briggs and Boone, 1988)
and

edge light pupil cycle time (Gibbons et al., 2000).

Table 4.
Studies of female
reproductive function.

Table 5.
Human studies of
somato-autonomic function.

The studies of skin conductance suggest that a sympathoexcitatory
effect can be induced in the lower limbs with lumbar
spinal manipulation (Perry et al., 2011), and perhaps in the hands
following mobilization of the thoracic region (Jowsey and Perry,
2010). The study by Perry et al. (2011) compared two interventions,
a ‘high-velocity low amplitude grade V manipulation’ of the lumbar
spine, and a set of lumbar extension exercises (25 subjects per cohort).
Both interventions produced a transient and statistically significant
increase in skin conductance, with the response to
manipulation being significantly larger than the response to exercise.
The study by Jowsey and Perry (2010) compared the effects of
a ‘grade III postero-anterior rotator joint mobilization technique applied
to the T4 vertebra’ with the effects of sustained pressure to the
same region (18 subjects per cohort). The sustained pressure resulted
in no changes in hand skin conductance whereas the mobilization
was accompanied by a slight increase in skin conductance in
one hand (p = 0.034 per one way ANOVA) but not the other; these
calculations based on percentage change from baseline.

Studies of the effects of spinal manipulation on the regulation of
pupil diameter report mixed results. Upper cervical manipulation
produced either increases or decreases in static pupil diameter in
individuals within a cohort of eight subjects who received spinal
manipulation, but no statistically significant change for the cohort
as a whole, a control cohort of seven subjects who did not receive
spinal manipulation also showed no change in pupillary diameter
over the 4-day course of the study. (Briggs and Boone, 1988). On
the other hand, in an uncontrolled study of a cohort of 13 young
men, upper cervical manipulation was also associated with a decrease
in edge light pupil cycle time (p = 0.002 per paired t-test);
i.e. the time it takes for the pupil to constrict and dilate following a
brief exposure to light. Thus, the manipulative procedure appeared
to accelerate the reflex response of the pupil, but it was not possible
to resolve specific effects on the parasympathetic vs. sympathetic
contributions to the reflex (Gibbons et al., 2000). While
these are intriguing human studies involving direct measures of
autonomically mediated responses to spinal manipulation, they
provide little physiological insight into the therapeutic impact of
spinal manipulation on visceral conditions.

Somato-humoural studies

The discussion so far has focused on studies of responses which
are most often presumed to be mediated by the autonomic nervous
system. However, responses to spinal manipulation may also be
mediated by other mechanisms, and a few studies have specifically
examined humoural and cellular mechanisms. Seven articles were
identified which measured such responses to spinal manipulation
in healthy cohorts (Table 6).

Table 6.
Somato-humoural studies

A controlled trial demonstrated that in a cohort (n = 27) of
healthy young males cervical manipulation was associated with a
statistically significant increase in plasma levels of the endogenous
analgesic beta-endorphin at 5 min post-treatment when measured
by radioimmune assay (Vernon et al., 1986). On the other hand, a
study of the effects of lumbar manipulation with a cohort of
asymptomatic subjects (n = 20) found no changes in beta-endorphin
levels at 5 and 30 min following treatment, nor changes in
serum cortisol (Christian et al., 1988). Whelan et al. (2002) also reported
no changes in salivary cortisol levels attributable to cervical
manipulation.

Early controlled studies also report that thoracic spinal manipulation
was associated with increased immune function, as measured
by zymosan-stimulated chemiluminescence, in neutrophils
and monocytes, and increased production of substance P and tumor
necrosis factor (TNF-a) at 15 min post treatment (Brennan
et al., 1991, 1992). On the other hand, a later and larger (n = 64)
controlled study using different methods of assay and a longer
time frame (up to 2 h) found that in healthy adults thoracic manipulation
was associated with a decrease in synthesis of TNF-a and
interleukin (IL-1b), and no change in levels of substance P (Teodorczyk-Injeyan
et al., 2006). The latter authors suggested that
such down regulation of inflammatory cytokines as they observed
was likely not mediated by substance P, but might have been the
result of activation of the parasympathetic nervous system. Using
a comparable design, they also demonstrated increased synthesis
of immunoglobulin G and immunoglobulin M at 20 min and 2 h,
respectively, following thoracic manipulation (Teodorczyk-Injeyan
et al., 2010). Collectively, these results do not paint a cohesive picture
of the effects of spinal manipulation on the complex interactions
within the immune system. Nonetheless, they do
demonstrate the phenomenon of immunological response to manual
therapy in the cohorts described.

Conclusions

Notwithstanding substantial interest by manual medicine practitioners
in somato-visceral disorders, there are relatively few basic
physiological studies in humans to guide clinical practice. The corpus
of somato-visceral studies is characterized by small cohorts of
subjects, uncontrolled trials and one time pilot exercises with no
subsequent follow-up. The field has been slow to adopt new technologies.
Only recently have teams of researchers appeared with
the sustained interest, expertise and resources to pursue meaningful
programmes of research. The greatest number of physiological
studies has focused on cardiovascular function, with few investigations
of other organ systems. There is a justifiable interest in autonomically-mediated
phenomena. However, somato-humoural and
non-autonomic neural mechanisms of spino-visceral interactions
remain largely unexplored.

Acknowledgements

P.S. Bolton’s research is supported by Grants from the National
Health and Medical Research Council of Australia and the Australian
Spinal Research Foundation.

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